Self-proteolysis regulation in the Bothrops jararaca venom: The metallopeptidases and their intrinsic peptidic inhibitor

Marques-Porto, Rafael; Lebrun, Ivo; Pimenta, Daniel C.

doi:10.1016/j.cbpc.2008.01.011

Cited by 22 publications

(18 citation statements)

References 32 publications

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“…Group II PLA 2 s can display a series of actions that result in toxic effects on victims such as myotoxicity [13], neurotoxicity [14], cytotoxicity [15,16] and genotoxicity [17][18][19]. Several studies focusing on the biological functions of PLA 2 s have discovered essential information of their implication in diseases such as rheumatoid arthritis, inflammation and bone erosion [20], cancer [21,22], and neurological disorders such as Alzheimer's disease, Parkinson's disease, multiple sclerosis, and epilepsy [23,24] There are also several studies investigating the antiparasitic effects of PLA 2 s against the parasites that cause leishmaniasis, Chahttp://dx.doi.org/10.1016/j.ijbiomac.2017.04.013 0141-8130/© 2017 Published by Elsevier B.V. gas disease and malaria.…”

Section: Introductionmentioning

confidence: 99%

BmajPLA 2 -II, a basic Lys49-phospholipase A 2 homologue from Bothrops marajoensis snake venom with parasiticidal potential

Grabner

Alfonso

Kayano

et al. 2017

International Journal of Biological Macromolecules

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Snake venoms contain various proteins, especially phospholipases A (PLAs), which present potential applications in diverse areas of health and medicine. In this study, a new basic PLA from Bothrops marajoensis with parasiticidal activity was purified and characterized biochemically and biologically. B. marajoensis venom was fractionated through cation exchange followed by reverse phase chromatographies. The isolated toxin, BmajPLA-II, was structurally characterized with MALDI-TOF (Matrix-assisted laser desorption/ionization-time of flight) mass spectrometry, sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE), followed by two-dimensional electrophoresis, partial amino acid sequencing, an enzymatic activity assay, circular dichroism, and dynamic light scattering assays. These structural characterization tests presented BmajPLA-II as a basic Lys49 PLA homologue, compatible with other basic snake venom PLAs (svPLA), with a tendency to form aggregations. The in vitro anti-parasitic potential of B. marajoensis venom and of BmajPLA-II was evaluated against Leishmania infantum promastigotes and Trypanosoma cruzi epimastigotes, showing significant activity at a concentration of 100μg/mL. The venom and BmajPLA-II presented IC of 0.14±0.08 and 6.41±0.64μg/mL, respectively, against intraerythrocytic forms of Plasmodium falciparum with CC cytotoxicity values against HepG2 cells of 43.64±7.94 and >150μg/mL, respectively. The biotechnological potential of these substances in relation to leishmaniasis, Chagas disease and malaria should be more deeply investigated.

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Section: Introductionmentioning

confidence: 99%

BmajPLA 2 -II, a basic Lys49-phospholipase A 2 homologue from Bothrops marajoensis snake venom with parasiticidal potential

Grabner

Alfonso

Kayano

et al. 2017

International Journal of Biological Macromolecules

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“…Protein Identifications in the Venoms Fractionated in the Presence of Proteinase Inhibitors-Viperid snake venoms possess high amounts of proteolytic enzymes (SVMPs and SVSPs), however there are protection mechanisms in the venom solution to avoid self-proteolysis (3,88,89). The proteolytic enzymes have optimal activity at alkaline pH (8 -9), whereas the pH of the venom solution is slightly acidic.…”

Section: De Novo Sequencing Of Peptides Present In the Venomsmentioning

confidence: 99%

“…Snake venoms also have a relatively high citrate concentration (30 to 150 mM), which should hamper the activity of metalloproteinases by chelating metal ions (3). In addition, viperid snake venoms also contain tri-peptides which inhibit metalloproteinase activity (4,89). Interestingly, these tri-peptides are encoded in the same mRNA of the BPP-CNP precursor and appear as short intervening sequences between the BPPs in the precursor (59).These protection mechanisms are no longer effective upon snake bite and venom injection into the prey because the venom is subjected to an environment suitable to the activity of SVMPs and SVSPs where the blood pH is slightly alkaline (7.35 to 7.45) and the concentrations of citrate ions and tri-peptides are lowered because of the venom spread and dilution process in the prey tissue.…”

Section: De Novo Sequencing Of Peptides Present In the Venomsmentioning

confidence: 99%

Peptidomics of Three Bothrops Snake Venoms: Insights Into the Molecular Diversification of Proteomes and Peptidomes

Tashima

Zelanis

Kitano

et al. 2012

Molecular & Cellular Proteomics

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Snake venom proteomes/peptidomes are highly complex and maintenance of their integrity within the gland lumen is crucial for the expression of toxin activities. There has been considerable progress in the field of venom proteomics, however, peptidomics does not progress as fast, because of the lack of comprehensive venom sequence databases for analysis of MS data. Therefore, in many cases venom peptides have to be sequenced manually by MS/MS analysis or Edman degradation. This is critical for rare snake species, as is the case of Bothrops cotiara (BC) and B. fonsecai (BF), which are regarded as near threatened with extinction. In this study we conducted a comprehensive analysis of the venom peptidomes of BC, BF, and B. jararaca (BJ) using a combination of solid-phase extraction and reversed-phase HPLC to fractionate the peptides, followed by nano-liquid chromatography-tandem MS (LC-MS/MS) or direct infusion electrospray ionization-(ESI)-MS/MS or MALDI-MS/MS analyses. We detected marked differences in the venom peptidomes and identified peptides ranging from 7 to 39 residues in length by de novo sequencing. Forty-four unique sequences were manually identified, out of which 30 are new peptides, including 17 bradykinin-potentiating peptides, three poly-histidine-poly-glycine peptides and interestingly, 10 L-amino acid oxidase fragments. Some of the new bradykinin-potentiating peptides display significant bradykinin potentiating activity. Automated database search revealed fragments from several toxins in the peptidomes, mainly from L-amino acid oxidase, and allowed the determination of the peptide bond specificity of proteinases and amino acid occurrences for the P4-P4 sites. We also demonstrate that the venom lyophilization/resolubilization process greatly increases the complexity of the peptidome because of the imbalance caused to the venom proteome and the consequent activity of proteinases on venom components. The use of proteinase inhibitors clearly showed different outcomes in the peptidome characterization and suggested that degradomic-peptidomic analysis of snake venoms is highly sensitive to the conditions of sampling procedures. Molecular & Cellular Proteomics 11: 10.1074/mcp.M112.019331, 1245-1262, 2012.Snake venoms are the products of specialized secretory glands located above the upper jawbone in venomous snakes. Like most secretory proteins, venom toxins are synthesized in the cytoplasm of secretory cells in the gland and transferred to the rough endoplasmic reticulum, then to the Golgi apparatus, and finally transported via secretory granules to the lumen of the venom gland (1). The snake venomous secretion is an aqueous solution containing a high amount of proteins and peptides, however the mechanisms for controlling protein secretion into the gland lumen and for regulating its protein/peptide concentration, ionic strength, and pH are unknown. As in all eukaryotic cells the proteomes of the venom gland tissue are highly complex, comprising a much great number and diversity of multidomain proteins (2...

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“…Estas proteínas são transferidas para o retículo endoplasmático rugoso, onde perdem o peptídeo sinal e assumem sua forma protéica através da formação de pontes de dissulfeto, glicosilações e multimerizações, como por exemplo, a dimerização de disintegrinas (P-IId/P-IIe) e adição de domínios tipo-lectina (P-IIId) (FOX e SERRANO, 2008b). No complexo de Golgi estas proteínas são transportadas em vesículas até o lúmen das glândulas secretoras (WARSHAWSKY et al, 1973;FOX e SERRANO, 2008b), onde o caráter ácido do meio, a presença de citrato e de tripeptídeos (piroGlu-Lys-Trp; piroGlu-Asn-Trp; piroGlu-Gln-Trp) (ROBEVA et al, 1991;ODELL et al, 1998;HUANG et al, 1998;MARQUES-PORTO et al, 2008) provavelmente inibem a atividade proteolítica destas enzimas no lúmen glandular mantendo a integridade celular e das proteínas do veneno.…”

Section: Metaloproteinases De Venenos De Serpentesunclassified

Estudo sobre a função dos domínios não catalíticos do HF3, uma metaloproteínase do veneno da serpente Bothrops jararaca, na sua interação com alvos celulares e plasmáticos.

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Self-proteolysis regulation in the Bothrops jararaca venom: The metallopeptidases and their intrinsic peptidic inhibitor

Cited by 22 publications

References 32 publications

BmajPLA 2 -II, a basic Lys49-phospholipase A 2 homologue from Bothrops marajoensis snake venom with parasiticidal potential

BmajPLA 2 -II, a basic Lys49-phospholipase A 2 homologue from Bothrops marajoensis snake venom with parasiticidal potential

Peptidomics of Three Bothrops Snake Venoms: Insights Into the Molecular Diversification of Proteomes and Peptidomes

Estudo sobre a função dos domínios não catalíticos do HF3, uma metaloproteínase do veneno da serpente Bothrops jararaca, na sua interação com alvos celulares e plasmáticos.

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